Agrin Inhibition in Enteric Neural Stem Cells Enhances Their Migration Following Colonic Transplantation.

Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.

Longitudinal Evaluation of a Statewide Quality Improvement Program for Nursing Homes.

OBJECTIVES: The National Academies of Sciences, Engineering, and Medicine (NASEM) Nursing Home Quality report recommends that states "develop and operate state-based…technical assistance programs…to help nursing homes…improve care and…operations." The Quality Improvement Program for Missouri (QIPMO) is one such program. This longitudinal evaluation examined and compared differences in quality measures (QMs) and nursing home (NH) characteristics based on intensity of QIPMO services used. DESIGN: A descriptive study compared key QMs of clinical care, facility-level characteristics, and differing QIPMO service intensity use. QIPMO services include on-site clinical consultation by expert nurses; evidence-based practice information; teaching NHs use of quality improvement (QI) methods; and guiding their use of Centers for Medicare and Medicaid Services (CMS)-prepared QM comparative feedback reports to improve care. SETTING AND PARTICIPANTS: All Missouri NHs (n = 510) have access to QIPMO services at no charge. All used some level of service during the study, 2020-2022. METHODS: QM data were drawn from CMS's publicly available website (Refresh April 2023) and NH characteristics data from other public websites. Service intensity was calculated using data from facility contacts (on-site visits, phone calls, texts, emails, webinars). NHs were divided into quartiles based on service intensity. RESULTS: All groups had different beginning QM scores and improved ending scores. Group 2, moderate resource intensity use, started with "worse" overall score and improved to best performing by the end. Group 4, most resource intensity use, improved least but required highest service intensity. CONCLUSIONS AND IMPLICATIONS: This longitudinal evaluation of QIPMO, a statewide QI technical assistance and support program, provides evidence of programmatic stimulation of statewide NH quality improvements. It provides insight into intensity of services needed to help facilities improve. Other states should consider QIPMO success and develop their own programs, as recommended by the NASEM report so their NHs can embrace QI and "initiate fundamental change" for better care for our nation's older adults.

Differentiated neuroblastoma cells remain epigenetically poised for de-differentiation to an immature state.

Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for a significant share of childhood cancer deaths. Prior studies utilizing RNA sequencing of bulk tumor populations showed two predominant cell states characterized by high and low expression of neuronal genes. Although cells respond to treatment by altering their gene expression, it is unclear whether this reflects shifting balances of distinct subpopulations or plasticity of individual cells. Using mouse and human neuroblastoma cell lines lacking MYCN amplification, we show that the antigen CD49b (also known as ITGA2) distinguishes these subpopulations. CD49b expression marked proliferative cells with an immature gene expression program, whereas CD49b-negative cells expressed differentiated neuronal marker genes and were non-cycling. Sorted populations spontaneously switched between CD49b expression states in culture, and CD49b-negative cells could generate rapidly growing, CD49b-positive tumors in mice. Although treatment with the chemotherapy drug doxorubicin selectively killed CD49b-positive cells in culture, the CD49b-positive population recovered when treatment was withdrawn. We profiled histone 3 (H3) lysine 27 acetylation (H3K27ac) to identify enhancers and super enhancers that were specifically active in each population and found that CD49b-negative cells maintained the priming H3 lysine 4 methylation (H3K4me1) mark at elements that were active in cells with high expression of CD49b. Improper maintenance of primed enhancer elements might thus underlie cellular plasticity in neuroblastoma, representing potential therapeutic targets for this lethal tumor.

Autism-Related Differences in Cortical Activation When Observing, Producing, and Imitating Communicative Gestures: An fNIRS Study.

Children with autism spectrum disorder (ASD) have difficulties in gestural communication during social interactions. However, the neural mechanisms involved in naturalistic gestural communication remain poorly understood. In this study, cortical activation patterns associated with gestural communication were examined in thirty-two children with and without ASD (mean age: 11.0 years, SE: 0.6 years). Functional near-infrared spectroscopy (fNIRS) was used to record cortical activation while children produced, observed, or imitated communicative gestures. Children with ASD demonstrated more spatial and temporal errors when performing and imitating communicative gestures. Although both typically developing (TD) children and children with ASD showed left-lateralized cortical activation during gesture production, children with ASD showed hyperactivation in the middle/inferior frontal gyrus (MIFG) during observation and imitation, and hypoactivation in the middle/superior temporal gyrus (MSTG) during gesture production compared to their TD peers. More importantly, children with ASD exhibited greater MSTG activation during imitation than during gesture production, suggesting that imitation could be an effective intervention strategy to engage cortical regions crucial for processing and producing gestures. Our study provides valuable insights into the neural mechanisms underlying gestural communication difficulties in ASD, while also identifying potential neurobiomarkers that could serve as objective measures for evaluating intervention effectiveness in children with ASD.

fNIRS-Based Differences in Cortical Activation during Tool Use, Pantomimed Actions, and Meaningless Actions between Children with and without Autism Spectrum Disorder (ASD).

Children with autism spectrum disorder (ASD) have difficulties with tool use and pantomime actions. The current study utilized functional near-infrared spectroscopy (fNIRS) to examine the neural mechanisms underlying these gestural difficulties. Thirty-one children with and without ASD (age (mean ± SE) = 11.0 ± 0.6) completed a naturalistic peg-hammering task using an actual hammer (hammer condition), pantomiming hammering actions (pantomime condition), and performing meaningless actions with similar joint motions (meaningless condition). Children with ASD exhibited poor praxis performance (praxis error: TD = 17.9 ± 1.7; ASD = 27.0 ± 2.6, p < 0.01), which was significantly correlated with their cortical activation (R = 0.257 to 0.543). Both groups showed left-lateralized activation, but children with ASD demonstrated more bilateral activation during all gestural conditions. Compared to typically developing children, children with ASD showed hyperactivation of the inferior parietal lobe and hypoactivation of the middle/inferior frontal and middle/superior temporal regions. Our findings indicate intact technical reasoning (typical left-IPL activation) but atypical visuospatial and proprioceptive processing (hyperactivation of the right IPL) during tool use in children with ASD. These results have important implications for clinicians and researchers, who should focus on facilitating/reducing the burden of visuospatial and proprioceptive processing in children with ASD. Additionally, fNIRS-related biomarkers could be used for early identification through early object play/tool use and to examine neural effects following gesture-based interventions.

Association for Academic Surgery/Society of University Surgeons research awards are highly successful in fostering future surgeon-scientists.

BACKGROUND: The surgeon-scientist brings a unique perspective to surgical research. The Association of Academic Surgeons and Society of University Surgeons foster the development of surgeon-scientists through foundation awards to residents and junior faculty. We sought to evaluate the academic success of surgeons who received an Association for Academic Surgery/Society of University Surgeons award. METHODS: Information was collected for individuals who received a resident or junior faculty research award from the Association for Academic Surgery or Society of University Surgeons. Google Scholar, Scopus, and the National Institutes of Health Research Portfolio Online Reporting Tools: Expenditures and Results were used to assess scholarly achievements. RESULTS: Eighty-two resident awardees were included, 31 (38%) of whom were female. Thirteen (24%) are now professors, 12 (22%) are division chiefs, and 4 (7%) are department chairs. Resident awardees have a median of 886 citations (interquartile range 237-2,111) and an H-index of 14 (interquartile range 7-23). Seven (13%) went on to receive K08/K23 awards, and 7 (13%) received R01s, with a total of about $200 million in National Institutes of Health funding (79-fold return on investment). Thirty-four junior faculty awardees were included, 10 (29%) of whom were female. Thirteen (38%) are now professors, 12 (35%) are division chiefs, and 7 (21%) are department chairs. Faculty awardees have a median of 2,617 citations (interquartile range 1,343-7,857) and an H-index of 25 (interquartile range 18-49). Four (12%) received K08 or K23 awards, and 10 (29%) received R01s, with about $139 million in National Institutes of Health funding (98-fold return on investment). CONCLUSION: Association for Academic Surgery/Society of University Surgeons research awardees experience high degrees of success in academic surgery. Most resident awardees pursue fellowship training and remain in academic surgery. A high percentage of both faculty and resident awardees hold leadership positions and successfully achieve National Institutes of Health funding.

Single-cell multiome sequencing clarifies enteric glial diversity and identifies an intraganglionic population poised for neurogenesis.

The enteric nervous system (ENS) consists of glial cells (EGCs) and neurons derived from neural crest precursors. EGCs retain capacity for large-scale neurogenesis in culture, and in vivo lineage tracing has identified neurons derived from glial cells in response to inflammation. We thus hypothesize that EGCs possess a chromatin structure poised for neurogenesis. We use single-cell multiome sequencing to simultaneously assess transcription and chromatin accessibility in EGCs undergoing spontaneous neurogenesis in culture, as well as small intestine myenteric plexus EGCs. Cultured EGCs maintain open chromatin at genomic loci accessible in neurons, and neurogenesis from EGCs involves dynamic chromatin rearrangements with a net decrease in accessible chromatin. A subset of in vivo EGCs, highly enriched within the myenteric ganglia and that persist into adulthood, have a gene expression program and chromatin state consistent with neurogenic potential. These results clarify the mechanisms underlying EGC potential for neuronal fate transition.

Bone Marrow Stem Cells Derived from Nerves Have Neurogenic Properties and Potential Utility for Regenerative Therapy.

Neurons and glia of the peripheral nervous system are derived from progenitor cell populations, originating from embryonic neural crest. The neural crest and vasculature are intimately associated during embryonic development and in the mature central nervous system, in which they form a neurovascular unit comprised of neurons, glia, pericytes, and vascular endothelial cells that play important roles in health and disease. Our group and others have previously reported that postnatal populations of stem cells originating from glia or Schwann cells possess neural stem cell qualities, including rapid proliferation and differentiation into mature glia and neurons. Bone marrow receives sensory and sympathetic innervation from the peripheral nervous system and is known to contain myelinating and unmyelinating Schwann cells. Herein, we describe a population of neural crest-derived Schwann cells residing in a neurovascular niche of bone marrow in association with nerve fibers. These Schwann cells can be isolated and expanded. They demonstrate plasticity in vitro, generating neural stem cells that exhibit neurogenic potential and form neural networks within the enteric nervous system in vivo following transplantation to the intestine. These cells represent a novel source of autologous neural stem cells for the treatment of neurointestinal disorders.

A distinct transcriptome characterizes neural crest-derived cells at the migratory wavefront during enteric nervous system development.

Enteric nervous system development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative ENCDCs at the wavefront, but the molecular characteristics of these cells are unknown. ENCDCs from the wavefront and the trailing region were isolated and subjected to RNA-seq. Wavefront-ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. This population of ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike trailing ENCDCs, the wavefront lacked expression of genes related to neuronal or glial maturation. As wavefront ENCDC genes were associated with migration and developmental immaturity, the genes that remain expressed in later progenitor populations may be particularly pertinent to understanding the maintenance of ENCDC progenitor characteristics. Dusp6 expression was specifically upregulated at the wavefront. Inhibiting DUSP6 activity prevented wavefront colonization of the hindgut, and inhibited the migratory ability of post-colonized ENCDCs from midgut and postnatal neurospheres. These effects were reversed by simultaneous inhibition of ERK signaling, indicating that DUSP6-mediated ERK inhibition is required for ENCDC migration in mouse and chick.

Sharing Lessons From Successes: Long-term Care Facilities That Weathered the Storm of COVID-19 and Staffing Crises.

PURPOSE: To identify leadership styles and staffing strategies in Missouri long-term care (LTC) facilities that stood out among their peers as "positive deviants" with regard to COVID-19 infections and staffing shortages. METHODS: Statewide survey of all LTC facilities to identify exemplar facilities with stable staffing and low rates of COVID-19. Interviews with senior leaders were conducted in 10 facilities in the state to understand the strategies employed that led to these "positive outliers." A result-based educational program was designed to describe their actions and staff reactions. RESULTS: Exemplar leaders used transformational leadership style. Top reasons for their success were as follows: (1) trusting and supportive staff relationships; (2) positive presence and communication; and (3) use of consistent staffing assignments. Strong statewide participation was noted in the educational programs.

Peripheral nervous system: A promising source of neuronal progenitors for central nervous system repair.

With a steadily aging population there is an increasing prevalence of neurological disorders. Given the lack of effective treatment strategies and a limited ability for the central nervous system (CNS) to regenerate endogenously, there is a critical need to better understand exogenous strategies for nervous system repair. Stem cell therapy offers a promising approach to promote the repair of neurologic tissue and function, however studies to date have been limited by various factors including challenges in harvesting donor cells from the CNS, ethical concerns regarding use of embryonic or fetal tissue, tumorigenic potential of induced pluripotent stem cells, and immune-mediated rejection of non-autologous cell sources. Here we review and propose two alternative sources of autologous cells derived from the peripheral nervous system (PNS) for CNS repair: enteric neuronal stem cells (ENSCs) and neural crest-derived Schwann cells found in subcutaneous adipose tissue (termed SAT-NSCs). ENSCs can be successfully isolated from the postnatal enteric nervous system, propagated in vitro, and transplanted successfully into models of CNS injury via both direct intracerebral injection and systemic tail vein injection. Similarly, SAT-NSCs can be readily isolated from both human and mouse adipose tissue and, although not yet utilized in models of CNS injury, have successfully been transplanted and restored function in models of colonic aganglionosis and gastroparesis. These unique sources of PNS-derived autologous cells offer an exciting option for stem cell therapies for the CNS as they have proven neurogenic potential and eliminate concerns around tumorigenic risk, ethical considerations, and immune-mediated rejection.

A pilot study characterizing longitudinal changes in fecal microbiota of patients with Hirschsprung-associated enterocolitis.

PURPOSE: Hirschsprung disease is a neurointestinal disease that occurs due to failure of enteric neural crest-derived cells to complete their rostrocaudal migration along the gut mesenchyme, resulting in aganglionosis along variable lengths of the distal bowel. Despite the effective surgery that removes the aganglionic segment, children with Hirschsprung disease remain at high risk for developing a potentially life-threatening enterocolitis (Hirschsprung-associated enterocolitis). Although the etiology of this enterocolitis remains poorly understood, several recent studies in both mouse models and in human subjects suggest potential involvement of gastrointestinal microbiota in the underlying pathogenesis of Hirschsprung-associated enterocolitis. METHODS: We present the first study to exploit the Illumina MiSeq next-generation sequencing platform within a longitudinal framework focused on microbiomes of Hirschsprung-associated enterocolitis in five patients. We analyzed bacterial communities from fecal samples collected at different timepoints starting from active enterocolitis and progressing into remission. RESULTS: We observed compositional differences between patients largely attributable to variability in age at the time of sample collection. Remission samples across patients exhibited compositional similarity, including enrichment of Blautia, while active enterocolitis samples showed substantial variability in composition. CONCLUSIONS: Overall, our findings provide continued support for the role of GI microbiota in the pathogenesis of Hirschsprung-associated enterocolitis.

The science of Hirschsprung disease: What we know and where we are headed.

The enteric nervous system (ENS) is a rich network of neurons and glial cells that comprise the gastrointestinal tract's intrinsic nervous system and are responsible for controlling numerous complex functions, including digestion, transit, secretion, barrier function, and maintenance of a healthy microbiome. Development of a functional ENS relies on the coordinated interaction between enteric neural crest-derived cells and their environment as the neural crest-derived cells migrate rostrocaudally along the embryonic gut mesenchyme. Congenital or acquired disruption of ENS development leads to various neurointestinal diseases. Hirschsprung disease is a congenital neurocristopathy, a disease of the neural crest. It is characterized by a variable length of distal colonic aganglionosis due to a failure in enteric neural crest-derived cell proliferation, migration, differentiation, and/or survival. In this review, we will review the science of Hirschsprung disease, targeting an audience of pediatric surgeons. We will discuss the basic biology of normal ENS development, as well as what goes awry in ENS development in Hirschsprung disease. We will review animal models that have been integral to studying this disease, as well as current hot topics and future research, including genetic risk profiling, stem cell therapy, non-invasive diagnostic techniques, single-cell sequencing techniques, and genotype-phenotype correlation.

Applications of Single-Cell Sequencing Technology to the Enteric Nervous System.

With recent technical advances and diminishing sequencing costs, single-cell sequencing modalities have become commonplace. These tools permit analysis of RNA expression, DNA sequence, chromatin structure, and cell surface antigens at single-cell resolution. Simultaneous measurement of numerous parameters can resolve populations including rare cells, thus revealing cellular diversity within organs and permitting lineage reconstruction in developing tissues. Application of these methods to the enteric nervous system has yielded a wealth of data and biological insights. We review recent papers applying single-cell sequencing tools to the nascent neural crest and to the developing and mature enteric nervous system. These studies have shown significant diversity of enteric neurons and glia, suggested paradigms for neuronal specification, and revealed signaling pathways active during development. As technology evolves and multiome techniques combining two or more of transcriptomic, genomic, epigenetic, and proteomic data become prominent, we anticipate these modalities will become commonplace in ENS research and may find a role in diagnostic testing and personalized therapeutics.

Review: Universal mental health interventions for young students in adverse environments - a systematic review of evaluated interventions.

BACKGROUND: Universal classroom-based interventions are a useful method to increase the mental health and resilience in children. Resilience describes the process that leads to a positive development despite adversities. It comprises the seven resources access to material resources, relationships, identity, power and control, cultural adherence, social justice and cohesion. Yet there is a paucity of studies evaluating interventions that enhance resilience in children exposed to adverse childhood experiences. METHOD: This systematic review investigates whether universal classroom-based interventions can increase the seven resilience-related resources in children that live in adverse environments. Search strings were formulated based on an adapted version of the PICO criteria. The risk of bias of the individual studies was assessed using the ROBINS-I tool. RESULTS: Seventeen studies were included in the review, of which 15 found an increase in resilience. The resource power and control was targeted in every intervention. Not one intervention included all seven resources. Intervention outcomes related mostly to just two of the resources (power and control and identity) and were rarely linked to what was being trained in the intervention. CONCLUSION: The results of this review show that classroom-based interventions are suitable for promoting resilience in children living in adverse environments. Yet more high-quality studies are needed that evaluate the effectiveness of universal interventions on children living in adverse environments and specifically the effectiveness of training each of the seven resources. Future developments of school-based interventions should be careful to target and assess all resilience-related resources.

Open hepatic resection in the elderly at two tertiary referral centers.

BACKGROUND: Surgeons are being increasingly called upon to operate on the very elderly. This study aimed to evaluate outcomes following hepatectomy in patients ≥80 years of age at two tertiary care centers. METHODS: All adult patients who underwent liver resection from 2001 to 2017 were included. Primary outcome was 90-day postoperative mortality. Secondary outcomes included 30-day postoperative mortality and postoperative complications. RESULTS: Between 2001 and 2017, 2397 patients underwent liver resection. On unadjusted analysis, patients ≥80 years of age had higher rates of 90-day mortality (13.3% vs. 3.6%, p < 0.001), 30-day mortality (5.6% vs. 1.8%, p = 0.01), MI (7.9% vs. 3.5%, p = 0.04), and UTI (10.0% vs. 4.5%, p = 0.02). On multivariable analysis, age ≥80 years was significantly associated with 90-day postoperative mortality (OR 4.51, 95%CI 2.11-9.67, p < 0.001). CONCLUSIONS: Across these two major referral tertiary care centers, very elderly patients had higher rates of 90-day and 30-day postoperative mortality on both unadjusted and adjusted analyses.

Differences in cortical activation patterns during action observation, action execution, and interpersonal synchrony between children with or without autism spectrum disorder (ASD): An fNIRS pilot study.

Engaging in socially embedded actions such as imitation and interpersonal synchrony facilitates relationships with peers and caregivers. Imitation and interpersonal synchrony impairments of children with Autism Spectrum Disorder (ASD) might contribute to their difficulties in connecting and learning from others. Previous fMRI studies investigated cortical activation in children with ASD during finger/hand movement imitation; however, we do not know whether these findings generalize to naturalistic face-to-face imitation/interpersonal synchrony tasks. Using functional near infrared spectroscopy (fNIRS), the current study assessed the cortical activation of children with and without ASD during a face-to-face interpersonal synchrony task. Fourteen children with ASD and 17 typically developing (TD) children completed three conditions: a) Watch-observed an adult clean up blocks; b) Do-cleaned up the blocks on their own; and c) Together-synchronized their block clean up actions to that of an adult. Children with ASD showed lower spatial and temporal synchrony accuracies but intact motor accuracy during the Together/interpersonal synchrony condition. In terms of cortical activation, children with ASD had hypoactivation in the middle and inferior frontal gyri (MIFG) as well as middle and superior temporal gyri (MSTG) while showing hyperactivation in the inferior parietal cortices/lobule (IPL) compared to the TD children. During the Together condition, the TD children showed bilaterally symmetrical activation whereas children with ASD showed more left-lateralized activation over MIFG and right-lateralized activation over MSTG. Additionally, using ADOS scores, in children with ASD greater social affect impairment was associated with lower activation in the left MIFG and more repetitive behavior impairment was associated with greater activation over bilateral MSTG. In children with ASD better communication performance on the VABS was associated with greater MIFG and/or MSTG activation. We identified objective neural biomarkers that could be utilized as outcome predictors or treatment response indicators in future intervention studies.

Randomized controlled trial of the Circle of Security-Intensive intervention for mothers with postpartum depression: maternal unresolved attachment moderates changes in sensitivity.

Postpartum depression is related to inadequately sensitive caregiving, putting infants at risk for insecure attachment. Therefore, promoting sensitive maternal caregiving and secure child attachment is particularly important in postpartum depressed mothers and their infants. In this randomized-controlled-trial, we evaluated the efficacy of the Circle of Security-Intensive (COS-I)-intervention in supporting maternal sensitivity and mother-infant-attachment compared to treatment-as-usual (TAU) with unresolved-maternal attachment as a moderator of treatment effect. Eligible mothers with infants (N=72) 4-9 months-old were randomly assigned to treatment (n=36 dyads). Infant attachment was rated at follow-up (child age 16-18 months) (Strange-Situation-procedure). Maternal sensitivity was measured at baseline and follow-up (Mini-Maternal-Behavior-Q-sort). Maternal-unresolved-attachment was assessed at baseline (Adult-Attachment-Interview). We found no significant differences between treatments in infant attachment nor changes in mothers' sensitivity. However, in COS-I, unresolved-mothers exhibited significantly more change in sensitivity than non-unresolved-mothers, whereas in TAU, the opposite was true. These findings may help to optimize clinical use of COS-I.

Is the Power Threshold of 0.8 Applicable to Surgical Science?-Empowering the Underpowered Study.

BACKGROUND: Many articles in the surgical literature were faulted for committing type 2 error, or concluding no difference when the study was "underpowered". However, it is unknown if the current power standard of 0.8 is reasonable in surgical science. METHODS: PubMed was searched for abstracts published in Surgery, JAMA Surgery, and Annals of Surgery and from January 1, 2012 to December 31, 2016, with Medical Subject Heading terms of randomized controlled trial (RCT) or observational study (OBS) and limited to humans were included (n = 403). Articles were excluded if all reported findings were statistically significant (n = 193), or if presented data were insufficient to calculate power (n = 141). RESULTS: A total of 69 manuscripts (59 RCTs and 10 OBSs) were assessed. Overall, the median power was 0.16 (interquartile range [IQR] 0.08-0.32). The median power was 0.16 for RCTs (IQR 0.08-0.32) and 0.14 for OBSs (IQR 0.09-0.22). Only 4 studies (5.8%) reached or exceeded the current 0.8 standard. Two-thirds of our study sample had an a priori power calculation (n = 41). CONCLUSIONS: High-impact surgical science was routinely unable to reach the arbitrary power standard of 0.8. The academic surgical community should reconsider the power threshold as it applies to surgical investigations. We contend that the blueprint for the redesign should include benchmarking the power of articles on a gradient scale, instead of aiming for an unreasonable threshold.